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J Clin Invest. 1986 June; 77(6): 1925–1930.
PMCID: PMC370553

Prevention of diabetic glomerulopathy by pharmacological amelioration of glomerular capillary hypertension.


Two groups of adult male Munich-Wistar rats and a third group of nondiabetic age-matched and weight-matched normal control rats underwent micropuncture study 1 mo, and morphologic studies 14 mo, after induction of streptozotocin diabetes or sham treatment. All animals were fed standard rat chow. Diabetic rats received daily ultralente insulin to maintain stable moderate hyperglycemia (approximately 350 mg/dl). In addition, one group of diabetic rats was treated with the angiotensin I converting enzyme inhibitor, enalapril, 15 mg/liter of drinking water. Average kidney weight, whole kidney and single-nephron glomerular filtration rate, and glomerular plasma flow rate were elevated to similar values in both groups of diabetic rats, relative to normal control rats. Non-enalapril-treated diabetic rats exhibited significant elevations in mean glomerular capillary hydraulic pressure and transcapillary hydraulic pressure gradient, compared with the other groups studied, and only this group eventually developed marked and progressive albuminuria. Likewise, histological examination of the kidneys at 14 mo disclosed a high incidence of glomerular structural abnormalities only in non-enalapril-treated diabetic rats. These findings indicate that prevention of glomerular capillary hypertension in rats with diabetes mellitus effectively protects against the subsequent development of glomerular structural injury and proteinuria. This protection is afforded despite pronounced hyperglycemia and elevated levels of glucosylated hemoglobin, further supporting our view that hemodynamic rather than metabolic factors predominate in the pathogenesis of diabetic glomerulopathy.

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Selected References

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  • STALDER G, SCHMID R. Severe functional disorders of glomerular capillaries and renal hemodynamics in treated diabetes mellitus during childhood. Ann Paediatr. 1959 Sep;193:129–138. [PubMed]
  • Mogensen CE. Glomerular filtration rate and renal plasma flow in short-term and long-term juvenile diabetes mellitus. Scand J Clin Lab Invest. 1971 Sep;28(1):91–100. [PubMed]
  • Christiansen JS, Gammelgaard J, Frandsen M, Parving HH. Increased kidney size, glomerular filtration rate and renal plasma flow in short-term insulin-dependent diabetics. Diabetologia. 1981 Apr;20(4):451–456. [PubMed]
  • Christiansen JS, Gammelgaard J, Tronier B, Svendsen PA, Parving HH. Kidney function and size in diabetics before and during initial insulin treatment. Kidney Int. 1982 May;21(5):683–688. [PubMed]
  • Hostetter TH, Troy JL, Brenner BM. Glomerular hemodynamics in experimental diabetes mellitus. Kidney Int. 1981 Mar;19(3):410–415. [PubMed]
  • Jensen PK, Christiansen JS, Steven K, Parving HH. Renal function in streptozotocin-diabetic rats. Diabetologia. 1981 Oct;21(4):409–414. [PubMed]
  • Zatz R, Meyer TW, Rennke HG, Brenner BM. Predominance of hemodynamic rather than metabolic factors in the pathogenesis of diabetic glomerulopathy. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5963–5967. [PubMed]
  • Hostetter TH, Rennke HG, Brenner BM. The case for intrarenal hypertension in the initiation and progression of diabetic and other glomerulopathies. Am J Med. 1982 Mar;72(3):375–380. [PubMed]
  • Zatz R, Brenner BM. Pathogenesis of diabetic microangiopathy. The hemodynamic view. Am J Med. 1986 Mar;80(3):443–453. [PubMed]
  • Hostetter TH, Olson JL, Rennke HG, Venkatachalam MA, Brenner BM. Hyperfiltration in remnant nephrons: a potentially adverse response to renal ablation. Am J Physiol. 1981 Jul;241(1):F85–F93. [PubMed]
  • Mogensen CE, Christensen CK. Predicting diabetic nephropathy in insulin-dependent patients. N Engl J Med. 1984 Jul 12;311(2):89–93. [PubMed]
  • Parving HH, Andersen AR, Smidt UM, Christiansen JS, Oxenbøll B, Svendsen PA. Diabetic nephropathy and arterial hypertension. The effect of antihypertensive treatment. Diabetes. 1983 May;32 (Suppl 2):83–87. [PubMed]
  • Drury PL. Diabetes and arterial hypertension. Diabetologia. 1983 Jan;24(1):1–9. [PubMed]
  • Rasch R. Control of blood glucose levels in the streptozotocin diabetic rat using a long-acting heat-treated insulin. Diabetologia. 1979 Mar;16(3):185–190. [PubMed]
  • Baylis C, Deen WM, Myers BD, Brenner BM. Effects of some vasodilator drugs on transcapillary fluid exchange in renal cortex. Am J Physiol. 1976 Apr;230(4):1148–1158. [PubMed]
  • Viets JW, Deen WM, Troy JL, Brenner BM. Determination of serum protein concentration in nanoliter blood samples using fluorescamine or 9-phthalaldehyde. Anal Biochem. 1978 Aug 1;88(2):513–521. [PubMed]
  • Mancini G, Carbonara AO, Heremans JF. Immunochemical quantitation of antigens by single radial immunodiffusion. Immunochemistry. 1965 Sep;2(3):235–254. [PubMed]
  • Garlick RL, Mazer JS, Higgins PJ, Bunn HF. Characterization of glycosylated hemoglobins. Relevance to monitoring of diabetic control and analysis of other proteins. J Clin Invest. 1983 May;71(5):1062–1072. [PMC free article] [PubMed]
  • Wallenstein S, Zucker CL, Fleiss JL. Some statistical methods useful in circulation research. Circ Res. 1980 Jul;47(1):1–9. [PubMed]
  • Steffes MW, Brown DM, Mauer SM. Diabetic glomerulopathy following unilateral nephrectomy in the rat. Diabetes. 1978 Jan;27(1):35–41. [PubMed]
  • Mauer SM, Steffes MW, Azar S, Sandberg SK, Brown DM. The effects of Goldblatt hypertension on development of the glomerular lesions of diabetes mellitus in the rat. Diabetes. 1978 Jul;27(7):738–744. [PubMed]
  • Parving HH, Smidt UM, Friisberg B, Bonnevie-Nielsen V, Andersen AR. A prospective study of glomerular filtration rate and arterial blood pressure in insulin-dependent diabetics with diabetic nephropathy. Diabetologia. 1981 Apr;20(4):457–461. [PubMed]
  • Wilson SK, Heptinstall RH. Effects of acute, angiotensin-induced hypertension on intrarenal arteries in the rat. Kidney Int. 1984 Mar;25(3):492–501. [PubMed]
  • Olson JL, de Urdaneta AG, Heptinstall RH. Glomerular hyalinosis and its relation to hyperfiltration. Lab Invest. 1985 Apr;52(4):387–398. [PubMed]
  • Williamson JR, Vogler NJ, Kilo C. Regional variations in the width of the basement membrane of muscle capillaries in man and giraffe. Am J Pathol. 1971 May;63(2):359–370. [PubMed]
  • Landis EM, Jonas L, Angevine M, Erb W. THE PASSAGE OF FLUID AND PROTEIN THROUGH THE HUMAN CAPILLARY WALL DURING VENOUS CONGESTION. J Clin Invest. 1932 Jul;11(4):717–734. [PMC free article] [PubMed]
  • Longhurst J, Capone RJ, Zelis R. Evaluation of skeletal muscle capillary basement membrane thickness in congestive heart failure. Chest. 1975 Feb;67(2):195–198. [PubMed]
  • Williamson JR, Kilo C. Current status of capillary basement-membrane disease in diabetes mellitus. Diabetes. 1977 Jan;26(1):65–73. [PubMed]
  • Nakamoto Y, Takazakura E, Hayakawa H, Kawai K, Dohi K, Fujioka M, Kida H, Hattori N, Takeuchi J. Intrarenal microaneurysms in diabetic nephropathy. Lab Invest. 1980 Apr;42(4):433–439. [PubMed]
  • Colwell JA, Halushka PV, Sarji K, Levine J, Sagel J, Nair RM. Altered platelet function in diabetes mellitus. Diabetes. 1976;25(2 Suppl):826–831. [PubMed]
  • Olson JL. Role of heparin as a protective agent following reduction of renal mass. Kidney Int. 1984 Feb;25(2):376–382. [PubMed]
  • Nakamoto Y, Dohi K, Fujike H, Yuri T, Shinoda A, Takeuchi J. Microangiographic evaluation of the effects of heparin on progressive Masugi nephritis. Kidney Int. 1978 Apr;13(4):297–305. [PubMed]
  • Baldwin DS. Chronic glomerulonephritis: nonimmunologic mechanisms of progressive glomerular damage. Kidney Int. 1982 Jan;21(1):109–120. [PubMed]
  • Viberti G, Keen H. The patterns of proteinuria in diabetes mellitus. Relevance to pathogenesis and prevention of diabetic nephropathy. Diabetes. 1984 Jul;33(7):686–692. [PubMed]
  • Ditzel J, Junker K. Abnormal glomerular filtration rate, renal plasma flow, and renal protein excretion in recent and short-term diabetics. Br Med J. 1972 Apr 1;2(5804):13–19. [PMC free article] [PubMed]

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